Integrative multi-omics characterization reveals sex differences in glioblastoma

Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults with limited treatment modalities and dismal prognosis. A thorough understanding of sex differences could facilitate personalized therapeutic strategies in GBM. In this study, we conducted a comprehensive multi-omics analysis from TCGA, CPTAC, and GLASS studies, revealing distinct molecular and clinical disparities between male and female GBM patients. We discovered that female GBM patients exhibited enrichments of MGMT promoter methylation and high genomic instability, including aneuploidy and TMB. While male GBMs were characterized by activation of EGFR protein and phosphorylation activities, female GBM patients demonstrated hyperphosphorylation of SPP1. Notably, these proteins demonstrated prognostic significance, highlighting their potential as therapeutic targets. Our findings provide unprecedented insights into the fundamental modulators of tumor progression and clinical outcomes in male and female GBM patients, offering valuable opportunities for sex-specific treatment interventions.